Cadmium

Cadmium (Cd) is a bluish white metal, soft and malleable. This metal and its byproducts are highly toxic to humans. Most of the cadmium produced today came from used nickel-cadmium batteries or from byproducts of zinc. Cd is an important metal for many industrial processes making industrial workers exposed to cadmium the more susceptible population. (1) Let’s discuss further its toxicity!

Source

Major sources of cadmium came from the industry processes that still use this metal. Manufacturing of batteries, solar panels and plastics as well as industry jobs like welding, painting, metal machining and electroplating are some of the major sources of cadmium. Workers in these industries can be exposed to toxicity by inhalation of fumes, mist or dusts containing cadmium. Exposure by ingestion of food or water contaminated with Cd and/or skin exposure are also possible. (1) As observed in image 1, Cd can also spread to soil, water, plantations and or animals by pollution in the areas near to its production or use. This makes possible the ingestion exposure by Cd contaminated food or water, exposing the population outside of the industry to its toxicity. (2)

Mechanism of Action and Biotransformation

In general, the mechanism of toxicity of cadmium is due to its ability to affect cell proliferation, differentiation and apoptosis. This effect can cause the creation of reaction oxygen species (ROS), can interfere with the mechanism of DNA repair and can induce apoptosis of healthy cells. (3) One of the major toxicities of Cd is to the kidneys (nephrotoxicity). The mechanism of nephrotoxicity happened after consumption of Cadmium in water or contaminated food getting into the blood. Once circulating in the blood, it binds to metallothionein which is a protein that helps remove toxic metals from the blood. This protein transports the Cadmium to the kidney’s glomerulus so it can be excreted from the body in the urine. Once the glomerulus filters the Cadmium and it enters the tubular cells, it is released and accumulates in the renal cortex instead of being excreted. When the accumulation reaches dangerous toxic levels, it deactivates metal-dependent enzymes which are important for mitochondrial function (the powerhouse of all cells) causing damage to the renal cells. (2)

Toxicokinetics

Cadmium has a limited gastrointestinal absorption (5-10%) after ingestion exposure, it has a greater absorption by inhalation exposure (10-60%). All of the cadmium that reaches the alveoli in the lung can be transferred to the blood facilitating the toxicity to other organs. Once in blood, Cd binds to proteins and is rapidly uptake by tissues ending up mainly in the liver or kidneys. Cd is transported into cells by calcium channels and molecular mimicry. Its half-life can be greater than 26 years and usually range from months to years depending on the severity of the exposure. Cadmium is poorly excreted after absorption by urine and feces, which explain the long half-life. (4)

Target Organ(s)

Cadmium reaches all the organs by transportation in the circulation and can be stored in the liver. Image 2 shows all the organs that can be affected by cadmium toxicity. The following organs received major toxic effects from Cd: kidneys, bones and lungs. The brain, heart, liver, reproductive organs and cells can also be affected by cadmium toxicity in minor levels. (5)

Signs and symptoms of toxicity (acute and chronic)

Acute exposure to cadmium by inhalation can cause irritation to the mucous membranes of the nose and upper respiratory tract. (5) Can also cause flu-like symptoms including chills, fever, muscle pain and pneumonia (1) Bone pain and weakness, early signs of renal damage (tubular dysfunction) and liver fibrosis can also occur.

With chronic exposure, toxicity to the lungs became lung disease consistent with emphysema. Bone damage evolves to bone deterioration, movement impairment and fractures. Renal damage can result in chronic kidney disease (CKD) and renal failure. Liver dysfunction, ischemic heart disease, cerebral infarction and neoplasms can also occur with chronic exposure to cadmium toxicity. (5)

Carcinogenicity

Cadmium may act as a carcinogen due to its cytotoxic effects when inhaled but there isn’t enough evidence of carcinogenic effects from ingestion exposure. Due to the cadmium ability to damage the DNA, induce apoptosis and necrotic events, and cause oxidative stress, it is associated with multiple types of cancer. More common types of cancer include lung, breast, prostate, pancreas, urinary bladder, nasopharynx and adenocarcinomas. (5)

Genetic susceptibility or heritable traits

Cadmium has the ability to cross the placenta causing teratogenic effects to fetus. Can also be a cause of pregnancy loss and can impair the development of the fetus. Cadmium also can cause irreparable damage to the DNA and can interact with multiple cell processes causing impairment in cell production. (5)

Treatments

Evaluation of the airways for inhalation exposure and irrigation of the gastrointestinal tract or gastric gavage for ingestion exposure are the first actions to be taken in the treatment of cadmium poisoning. Evaluation of the status of liver, lungs and kidneys is also important to provide supporting treatments to the patient to prevent the progression of the damage to these major organs. The use of chelating therapy is the main treatment used for cadmium poisoning. Chelating therapy can also be combined with other substances to obtain better results. The use of antioxidants like vitamin C and E can provide protection against cadmium toxicity. The use of vitamin A, C, E and selenium has been proved to reduce the toxic effects of cadmium in the liver, kidneys, skeleton and blood. Zinc and magnesium can reverse the renal toxicity caused by cadmium. (3)

Essentiality and deficiency

Cadmium is not an essential metal for humans. It is highly toxic, and exposure should be avoided.

Historical or unique exposure

Cadmium is well known for a big exposure in the 1900’s in Toyama Japan due to mining. This exposure contaminates the Jinzu river poisoning the water and rice crops in the area causing all the nearby population to get sick. The chronic cadmium poisoning was then identified and recognized as Itai-Itai diseased (meaning ouch-ouch) due to the painful effects to the bones. (2) The following video explains more in detail the story of Itai-Itai disease and how was linked to cadmium poisoning. I also invite you to visit my page about the same topic to learn more about the effect of the disease in the renal system, using the following link: https://new.express.adobe.com/webpage/Jt5KghA21jp3n.

References

1.US Department of Labor. (n.d.). Cadmium. Retrieved from Occupational Safety and Health Administration (OSHA): https://www.osha.gov/cadmium

2. Grover, N. (2024). Itai-itai Disease – Environment Notes. Retrieved from Prepp by Collegedunia: https://prepp.in/news/e-492-itai-itai-disease-environment-notes

3. Rafati Rahimzadeh, M., Kazemi, S., & Moghadamnia, A. A. (2017). Cadmium toxicity and treatment: An update. Caspian journal of internal medicine, 8(3), 135–145. https://doi.org/10.22088/cjim.8.3.135

4. Ufelle A.C., & Barchowsky A. (2019). Toxic effects of metals. Klaassen C.D.(Ed.), Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th edition. McGraw-Hill Education. https://accesspharmacy-mhmedical-com.proxy.lib.ohio-state.edu/content.aspx?bookid=2462&sectionid=202676441

5. Charkiewicz A.E., Omeljaniuk W.J., Nowak K., Garley M., & Nikliński J. (2023). Cadmium Toxicity and Health Effects—A Brief Summary. Molecules, 28(18), 6620. https://doi.org/10.3390/molecules28186620

6. Geopop, everyday science. (2024, January 8). “The Cadmium Mystery in Japan: The Strange ITAI-ITAI Disease with an Unexpected Origin” [Video]. YouTube. https://www.youtube.com/watch?v=-T87ywbaKkg